Chloé Michaudel1, Claire Mackowiak1, Isabelle Maillet1, Louis Fauconnier2, Cezmi A Akdis3, Milena Sokolowska3, Anita Dreher3, Hern-Tze Tina Tan4, Valérie F Quesniaux1, Bernhard Ryffel5, Dieudonnée Togbe6. 1. Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans, France. 2. ArtImmune SAS, Orleans, France. 3. Swiss Institute for Allergy and Asthma Research and Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. 4. Swiss Institute for Allergy and Asthma Research and Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia. 5. Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans, France; Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC), Immunology and Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Clinical Immunology, Third Hospital at Sun Yat-sen University Guangzhou, Guangzhou, China. Electronic address: bryffel@cnrs-orleans.fr. 6. Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans, France; ArtImmune SAS, Orleans, France. Electronic address: dtogbe@cnrs-orleans.fr.
Abstract
BACKGROUND: IL-33 plays a critical role in regulation of tissue homeostasis, injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions independently of airways hyperresponsiveness (AHR) in the setting of ozone-induced lung injury and inflammation is unclear. OBJECTIVE: We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice. METHODS: ST2- and Il33-deficient, IL-33 citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined. RESULTS: We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouse IL-33 reduced neutrophil recruitment in Il33-deficient mice. CONCLUSION: Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell-mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation.
BACKGROUND:IL-33 plays a critical role in regulation of tissue homeostasis, injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions independently of airways hyperresponsiveness (AHR) in the setting of ozone-induced lung injury and inflammation is unclear. OBJECTIVE: We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice. METHODS:ST2- and Il33-deficient, IL-33citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined. RESULTS: We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouseIL-33 reduced neutrophil recruitment in Il33-deficient mice. CONCLUSION: Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell-mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation.
Authors: Jonathan M Carnino; Heedoo Lee; Ley Cody Smith; Vasanthi R Sunil; Raymond C Rancourt; Kinal Vayas; Jessica Cervelli; Zhi Hao Kwok; Kareemah Ni; Jeffrey D Laskin; Yang Jin; Debra L Laskin Journal: Toxicol Sci Date: 2022-04-26 Impact factor: 4.109
Authors: Youngji Cho; Galeb Abu-Ali; Hiroki Tashiro; Traci A Brown; Ross S Osgood; David I Kasahara; Curtis Huttenhower; Stephanie A Shore Journal: Am J Respir Cell Mol Biol Date: 2019-02 Impact factor: 6.914